This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Streptococcus mutans is considered as the major etiological agent in dental caries. S. mutans is also an important agent of infective endocarditis. The organism colonizes the oral cavity by forming diverse, multispecies biofilms on the tooth surface, known as dental plaque. This pathogen has developed multiple mechanisms to adapt and to flourish in the hostile environment of the oral cavity. S. mutans has the ability to respond rapidly and efficiently to various environmental fluxes, including severe nutrient limitation, fluctuations in pH and temperature, and changes in oxidative and osmotic tensions. Exposure of bacteria to these adverse environments can induce a stress tolerance response through expression of a wide variety of genes that provides cross-protection against diverse environmental challenges. Stress tolerance genes are regulated by unique groups of transcriptional regulators, including alternate sigma factors. However, unlike other pathogens, S. mutans and other streptococci do not encode any alternate sigma factors. On the other hand, some genes that putatively function in stress responses in other bacteria are present in the S. mutans genome, but their role in stress and virulence has not been investigated in S. mutans in great detail. In this project, we plan to identify genes that are necessary for the organism to survive in the hostile environment of the oral cavity to cause tooth decay. Successful completion of our studies may lead to the development of novel therapeutic treatments for the prevention of tooth decay.